Conclusions
PEG-ADA treatment of ADA-deficient mice will serve as a useful in vivo system to biochemically manipulate adenosine levels and signaling. The fact that correction of adenosine levels corresponds with relief of the pulmonary distress, but not immune dysfunction, in ADA-deficient mice suggests that hyperactive adenosine signaling influences the eosinophilia, elevated IgE levels, alveolar defects, and severe inflammation and damage seen in the lungs of the mice. 26
High adenosine levels in bronchial alveolar lavage fluid (BALF) of asthmatics and other evidence strongly links dysfunctional adenosine signaling to asthma, chronic obstructive pulmonary disease (COPD), and other pulmonary disorders27. It is likely that other phenotypical features seen in ADA deficiency may have abnormal adenosine signaling as their effector. Just as varying concentrations of antigen binding to the T cell receptor (TCR) complex determine the destiny of a T cell (apoptosis, anergy, activation, or proliferation), varying amounts of adenosine interacting with adenosine receptors could affect the survival or actions of cells expressing the receptors. ADA-deficient mice, treated with varying regimens of PEG-ADA, will provide an ideal model in which to study adenosine signaling through adenosine receptors.
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Aldrich, M.B., Blackburn, M.R., Datta, S.K., Kellems, R.E. (2002). Adenosine Deaminase-Deficient Mice: Models for the Study of Lymphocyte Development and Adenosine Signaling. In: Zoref-Shani, E., Sperling, O. (eds) Purine and Pyrimidine Metabolism in Man X. Advances in Experimental Medicine and Biology, vol 486. Springer, Boston, MA. https://doi.org/10.1007/0-306-46843-3_11
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